Evidence map›Paper›PMID 28841717›Full record

ArticlePLoS pathogens2017

Streptococcus pneumoniae in the heart subvert the host response through biofilm-mediated resident macrophage killing.

Anukul T Shenoy, Terry Brissac, Ryan P Gilley, Nikhil Kumar, Yong Wang, Norberto Gonzalez-Juarbe, Whitney S Hinkle, Sean C Daugherty, Amol C Shetty, Sandra Ott and 4 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
5.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Heme-mediated selection of encapsulatedEmerging microbes & infections · 2025
    Article
  8. Pneumococcal HbioRxiv : the preprint server for biology · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Pneumococcal Endocarditis: Historical Insights and Modern Challenges.Journal of community hospital internal medicine perspectives · 2025
    Article
  14. Infectious factors in myocarditis: a comprehensive review of common and rare pathogens.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2024
    Review
  15. Article
  16. The inflammatory spectrum of cardiomyopathies.Frontiers in cardiovascular medicine · 2024
    Review
  17. Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Anukul T ShenoyDepartment of Microbiology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
Terry BrissacDepartment of Microbiology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.ORCID http://orcid.org/0000-0002-2549-4479
Ryan P GilleyDepartment of Microbiology, Immunology, and Molecular Genetics, The University of Texas Health San Antonio, San Antonio, TX, United States of America.
Nikhil KumarDepartment of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States of America.
Yong WangDivision of Pulmonary, Allergy & Critical Care Medicine, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
Norberto Gonzalez-JuarbeDepartment of Microbiology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
Whitney S HinkleDepartment of Microbiology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
Sean C DaughertyDepartment of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States of America.
Amol C ShettyDepartment of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States of America.
Sandra OttDepartment of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States of America.
Luke J TallonDepartment of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States of America.ORCID http://orcid.org/0000-0002-4656-4480
Jessy DeshaneDivision of Pulmonary, Allergy & Critical Care Medicine, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
Hervé TettelinDepartment of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States of America.
Carlos J OrihuelaDepartment of Microbiology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.ORCID http://orcid.org/0000-0002-8542-4069
University of Maryland, Baltimore · USUniversity of Alabama at Birmingham · USThe University of Texas Health Science Center at San Antonio · US

Funding

IMMUNOLOGIC DISEASES AND BASIC IMMUNOLOGYT32AI007051 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Laurie Ellen Harrington · 1985 to 2026
$13.1M
Mentored Experiences in Research, Instruction and Teaching (MERIT) Program - administrative supplementK12GM088010 · NIGMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SCHNEIDER, DAVID ALAN · 2009 to 2024
$9.2M
Cardiac microlesion formation during invasive pneumococcal diseaseR01AI114800 · NIAID · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Carlos J Orihuela, Herve S TETTELIN · 2015 to 2026
$5.1M
Myeloid-Derived Regulatory Cells in AsthmaR01HL128502 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DESHANE, JESSY SATYADAS · 2016 to 2020
$1.8M
NHLBI NIH HHS R01 HL128502NIAID NIH HHS R01 AI114800NIAID NIH HHS T32 AI007051NIGMS NIH HHS K12 GM088010
6 · The paper itself

Abstract

For over 130 years, invasive pneumococcal disease has been associated with the presence of extracellular planktonic pneumococci, i.e. diplococci or short chains in affected tissues. Herein, we show that Streptococcus pneumoniae that invade the myocardium instead replicate within cellular vesicles and transition into non-purulent biofilms. Pneumococci within mature cardiac microlesions exhibited salient biofilm features including intrinsic resistance to antibiotic killing and the presence of an extracellular matrix. Dual RNA-seq and subsequent principal component analyses of heart- and blood-isolated pneumococci confirmed the biofilm phenotype in vivo and revealed stark anatomical site-specific differences in virulence gene expression; the latter having major implications on future vaccine antigen selection. Our RNA-seq approach also identified three genomic islands as exclusively expressed in vivo. Deletion of one such island, Region of Diversity 12, resulted in a biofilm-deficient and highly inflammogenic phenotype within the heart; indicating a possible link between the biofilm phenotype and a dampened host-response. We subsequently determined that biofilm pneumococci released greater amounts of the toxin pneumolysin than did planktonic or RD12 deficient pneumococci. This allowed heart-invaded wildtype pneumococci to kill resident cardiac macrophages and subsequently subvert cytokine/chemokine production and neutrophil infiltration into the myocardium. This is the first report for pneumococcal biofilm formation in an invasive disease setting. We show that biofilm pneumococci actively suppress the host response through pneumolysin-mediated immune cell killing. As such, our findings contradict the emerging notion that biofilm pneumococci are passively immunoquiescent.

Indexed as

BiofilmsTranscriptomeAnimalsBlotting, WesternDisease Models, AnimalFemaleFlow CytometryFluorescent Antibody TechniqueGene Expression ProfilingMacrophagesMiceMice, Inbred BALB CMicroscopy, Electron, TransmissionMyocarditisPneumococcal InfectionsPrincipal Component Analysis

Identifiers

PMID28841717
PMCPMC5589263
OpenAlexW2748371959

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.